The purpose of this proposal is to analyze the changes in gene expression profiles during the mammalian cell cycle, distinguish the genes necessary for cell cycle progression from the genes that characterize the serum response, and separate the tissue specific cell cycle genes from the core cell cycle machinery. CDNA microarrays will be used to measure the expression of more than 20,000 different genes during cell cycle progression. Using hierarchical clustering algorithms the genes with similar expression patterns can be placed into gene clusters which generally contain genes of similar function. Characterization of the gene expression changes that occur during the eukaryotic cell cycle will allow me to define clusters of co-regulated genes, assign unknown genes to specific clusters and potentially define new cell cycle regulated circuitry which could help define targets for drug discovery and molecular markers for different phases of the cell cycle. Aim 1. Characterization of the gene expression program during the cell growth and proliferation. Gene expression will be measure in cells synchronized by various methods. Aim 2. Dissection of the mammalian serum response. Gene expression will be measured during stimulation with different mitogens. Aim 3. Characterization of the core cell cycle genes and tissue specific gene expression. The above analyses will be performed in different tissues and data analyzed by clustering.